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Background/aim: Chemoresistance to paclitaxel (PTX) significantly ameliorates therapeutic efficacy in patients with non-small cell lung cancer (NSCLC), especially in advanced stages, deteriorating the progression free and overall survival rates. One of the critical mechanisms contributing to drug resistance is the excretion of PTX from target cells via efflux pumps. Ivermectin was developed as a bactericidal agent against parasites; however, it has recently been shown to inhibit the proliferation of human cancer cells. Hence, we aimed to evaluate the therapeutic potential of ivermectin in combination with PTX and investigate the molecular mechanisms by which ivermectin overcomes PTX resistance., Materials and Methods: We assessed the antitumor effects of ivermectin in A549 cells treated with or without PTX. We also established PTX-resistant cells using this cell line and explored the underlying mechanisms. Additionally, we evaluated whether ivermectin attenuates PTX-resistance with the retrieval of drug sensitivity., Results: Combined treatment of A549 cells with PTX and ivermectin inhibited cell growth. These cells acquired chemoresistance upon long-term exposure to gradually increasing PTX concentrations, which was accompanied by ABCB1 mRNA up-regulation, and subsequent overproduction of P-glycoprotein (P-gp). Consistent with this, P-gp over-expression resulted in a PTX-resistant phenotype. Notably, the simultaneous ivermectin treatment during the gradual exposure completely abolished P-gp expression, leading to an increased intracellular PTX concentration and sustained PTX sensitivity. Ivermectin was found to regulate P-gp expression via the EGFR/ERK/Akt/NF-[Formula: see text]B pathway., Conclusion: Combined treatment of PTX-resistant A549 cells with ivermectin and PTX may circumvent PTX resistance caused by P-gp induction, highlighting a novel therapeutic avenue for drug repurposing., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Necitumumab plus gemcitabine and cisplatin (GCN) is a standard therapy for patients with advanced lung squamous cell carcinoma (LSqCC). However, the efficacy and tolerability of GCN in second-line or later treatment for patients previously treated with immune checkpoint inhibitors (ICIs) remain unknown., Methods: This multicenter, retrospective, cohort study assessed the efficacy and tolerability of GCN initiated between November 1, 2019 and March 31, 2022 as second-line to fourth-line treatment in patients with advanced LSqCC who had been pretreated with ICIs. The primary end point was progression-free survival (PFS)., Results: A total of 93 patients from 35 institutions in Japan were enrolled. The median PFS, median overall survival (OS), and objective response rate were 4.4 months (95% confidence interval [CI]: 3.8-5.3), 13.3 months (95% CI: 9.6-16.5), and 27.3% (95% CI: 18.3-37.8), respectively. The median PFS, median OS, and objective response rate for second-line, third-line, and fourth-line treatment groups were 4.8 months, 3.8 months, and 4.3 months ( p  = 0.24); 15.7 months, 11.6 months, and 10.1 months ( p  = 0.06); and 31.0%, 13.6%, and 37.5% ( p  = 0.22), respectively. The severity of GCN-related skin disorders was associated with longer PFS ( p < 0.05) and OS ( p < 0.05). The frequencies of grade ≥3 skin disorders, hypomagnesemia, pneumonitis, and febrile neutropenia were 16.1%, 7.5%, 1.1%, and 4.3%, respectively. There were no treatment-related deaths., Conclusions: GCN for ICI-pretreated patients with LSqCC seems tolerable and offers promising efficacy regardless of treatment line, and ICI pretreatment might enhance GCN efficacy., (© 2023 The Authors.)

Adenoid cystic carcinoma (ACC) is a rare type of malignant tracheal tumor originating from the secretory glands. Complete surgical resection is the current standard of care for tracheal ACC. However, there have been few case reports of chemoradiotherapy for unresectable tracheal ACC. We herein report a 28-year-old man with unresectable tracheal ACC who received concurrent chemoradiotherapy (CCRT) followed by maintenance therapy with durvalumab. CCRT was completed with a good response and safety, and the patient is currently receiving durvalumab as maintenance therapy. Durvalumab after CCRT can be a treatment option for patients with unresectable tracheal ACC.

Pulmonary involvement associated with inflammatory bowel disease (IBD) are a rare extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), we herein presented two cases. Case 1: 53-year-old man with Crohn's disease treated with mesalazine and azathioprine. Pulmonary nodular shadows were incidentally detected on chest imaging, and revealed granulomas through transbronchial lung biopsy. Case 2: 68-year-old man with ulcerative colitis treated with mesalazine. He presented with fever and respiratory symptoms, and chest imaging showed multiple nodular infiltrates. He was diagnosed with organizing pneumonia by lung biopsy. Both cases were diagnosed to have pulmonary involvement associated with inflammatory bowel disease (IBD) according to multidisciplinary examination including positron emission tomography-computed tomography (FDG-PET) and pathological test. Pulmonary manifestations with IBD may not always require discontinuation of drugs or additional use of steroids or immunosuppressants., Competing Interests: None., (© 2023 The Authors.)

Background: Amrubicin (AMR) is one of the most active agents for small-cell lung cancer (SCLC). However, hematologic toxicity and infection at a commonly used dose (40 mg/m 2 ) is problematic; the optimal dose remains undetermined., Patients and Methods: To evaluate the optimal dose of AMR in terms of efficacy and safety, we reviewed consecutive data on patients with relapsed SCLC who received AMR at doses of 40, 35, and 30 mg/m 2 (on days 1-3) at Nippon Medical School Hospital between October 2010 and November 2021., Results: We reviewed the data of 86 patients (20, 45, 27 who received AMR doses of 40, 35, 30 mg/m 2 , respectively) according to our study criteria. For patients  ≥ 75 years, the proportion who received second-line treatment tended to be higher in the 30-35 mg/m 2 group. Objective response rates were 37/46/35%, median progression-free survival (PFS) were 3.0/4.7/3.2 months, and median overall survival (OS) were 7.8/16.3/8.0 months, respectively. Grade 4 neutropenia occurred in 58/39/31% of patients, which was higher for the 40 mg/m 2 group. The incidence of febrile neutropenia did not differ between groups. Multivariate analysis identified the AMR dose was not associated with longer PFS and OS., Conclusion: Treatment with AMR between 30 and 35 mg/m 2 showed relatively mild hematologic toxicity compared with AMR at 40 mg/m 2 , without any significant difference in efficacy. Lower dose of AMR for relapsed SCLC could be a promising treatment option., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Pembrolizumab is an immune checkpoint inhibitor (ICI) that targets programmed death-1. Although ICIs have shown efficacy in the treatment of lung cancer, they have also been reported to cause a variety of immune-related adverse events (irAEs). Hepatotoxicity is a known irAEs, but currently, there is not enough information on its pathological characteristics and treatment. We report the case of a 70-year-old man with advanced squamous-cell lung cancer who developed severe grade 4 hepatitis on day 8 after receiving carboplatin, nab-paclitaxel, and pembrolizumab as fourth-line therapy. We treated him with steroid therapy the day after a liver biopsy was performed to investigate his pathological features, which led to a rapid and remarkable improvement. Confirmation of immune-related hepatotoxicity by pathological findings allowed the early tapering and discontinuation of steroid therapy. Performing a liver biopsy and verifying histological characteristics are needed for successful treatment with short-term steroids when drug-induced hepatitis caused by anti-cancer therapy including pembrolizumab is considered., Competing Interests: Prof. Dr. Kaoru Kubota reports personal fees from Chugai, personal fees from Taiho, personal fees from MSD, grants, personal fees from Boehringer Ingelheim, personal fees from AstraZeneca, personal fees from Bristol Myers Squibb, personal fees from Eli-Lilly, personal fees from Daiichi Sankyo, grants, personal fees from Ono, personal fees from Kirin, personal fees from Eisai, personal fees from Shionogi, personal fees from Nippon Kayaku, outside the submitted work. Dr Masahiro Seike reports grants, personal fees from MSD K.K, grants, personal fees from Taiho Pharmaceutical, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2022 Hayashi et al.)

A 59-year-old woman complaining of wet cough, hemoptysis, slight fever, anorexia, and malaise was admitted to hospital with suspected lobar pneumonia. She received treatment for myocardial infarction and deep venous thrombosis caused by familial protein C deficiency. Rapid deterioration due to respiratory failure occurred despite intensive care with broad-spectrum antibiotics. At a later date, sputum examination revealed the presence of Aspergillus niger . Based on clinical and autopsy findings, she was diagnosed with acute respiratory failure due to pulmonary aspergillosis with acute fibrinous and organizing pneumonia. This is the first reported case of pulmonary aspergillosis with acute fibrinous and organizing pneumonia complicated by calcium oxalate resulting from Aspergillus niger infection, leading to severe inflammation and tissue injury in the lungs., Competing Interests: The authors declare that they do not have any conflict of interest., (© 2022 The Authors. Published by Elsevier Ltd.)

Competing Interests: Competing interests: None declared.

Background: Patients with heart failure (HF) accompanied by delirium are at risk of rehospitalization and death, thus early detection and appropriate treatment is imperative. Palliative care for patients with HF is an important issue, particularly for patients who also have delirium. This retrospective study examined the accuracy of delirium assessment by cardiologists treating patients with HF, identified factors related to the detection of delirium, and recorded the initial treatment., Methods: This was a retrospective chart survey of 165 patients with HF referred to a consultation liaison (C-L) service during treatment in the cardiology wards of a general hospital over a 6-year period. Diagnosis of delirium by the C-L psychiatrists was based on DSM-IV-TR.Cases in which cardiologists had stated "delirium" in the medical records were classified as an accurate assessment of delirium (Agreement group). Cases in which cardiologists did not state "delirium" were classified as Disagreement., Results: Among 81 patients with delirium (51 [62.9%] male; 74.7 ± 13.3 years old), the ratio of accurate assessment of delirium by cardiologists was 50.6% ( n  = 41; Agreement group). Age, sex, and HF severity did not differ significantly between the two groups. Although disquietedness was identified most frequently ( n  = 59, 73%), only 33 of these 59 patients (55.9%) were recognized as having delirium by cardiologists.Inappropriate initial treatments were only noted in the Disagreement group. In both groups, most cases were referred to a C-L service without new medication for psychiatric symptoms., Conclusions: An accurate assessment of the delirium of inpatients with HF by cardiologists was found in only around half of all cases. Accurate detection is important to avoid harmful drug administration and to provide appropriate palliative care., Competing Interests: Competing interestsAll authors declare no conflicts of interest related to this study. SK has received speaker’s honoraria from Bayer, Otsuka, Eisai, Chugai and MSD, outside the submitted work. AH reports personal fees from Meiji Seika Pharma, Mochida, Yoshitomiyakuhin, Shinkoh-igaku Publishers and Japan Medical Journal, outside the submitted work. KM has received speaker’s honoraria from Eisai, Meiji Seika Pharma, Mochida, MSD, Otsuka, and Yoshitomiyakuhin, and a research grant from Ministry of Education, Culture, Sports, Science and Technology, outside the submitted work. RA has received personal fees from Cancer Patients Support Organization, Jiho, Ishiyaku Publishers, Igaku-Shoin, Kagakuhyoronsha, Gakken, Seiwa Shoten Publishers, Yoshitomiyakuhin, and Chugai Pharma, outside the submitted work. NK has received speaker’s honoraria from Meiji Seika Pharma, Mochida, Takeda, Yoshitomiyakuhin, Pfizer, Eli Lilly, MSD, Shionogi, Janssen, Eisai, Astellas, Otsuka, Daiichi Sankyo, Nipro, Kissei, Tsumura, Novartis, Mitsubishi Tanabe, and Chugai; he has received research/grant support from Mochida, Takeda, Otsuka, Novartis, Mitsubishi Tanabe, Dainippon Sumitomo, MSD, Eisai, Tsumura, Eli Lilly, GlaxoSmithKline, and Mebix within the past 3 years outside the submitted work., (© The Author(s) 2020.)